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The Plasmodium falciparum genome project: A resource for researchers

Almost 5 years ago, an international consortium of sequencing centers and funding agencies was formed to sequence the genome of the human malaria parasite Plasmodium falciparum. A novel chromosome by chromosome shotgun strategy was devised to sequence this very AT-rich genome. Two of the 14 chromosomes have been completed and the remaining chromosomes are in the final stages of gap closure. The consortium recently developed plans for the annotation and analysis of the complete genome sequence and its publication in 2002.

The polymorphic multigene family, var, encodes the variant antigen, Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1), present on the surface of erythrocytes infected with the human malaria parasite, P. falciparum. PfEMP1 has been implicated in the pathology of malaria through its ability to bind to host endothelial receptors and uninfected erythrocytes. Understanding the relationship between host pathology, immune response and parasite variation is crucial, but requires a method of reliably detecting and differentiating all possible var genes. Several primer pairs used to date are biased and limited in their detection capacity. Here we describe a set of PCR primers that amplify the majority of var genes in the laboratory isolates 3D7 and A4, and appear to work equally well on all isolates tested. We use these universal primers to examine the relationship between var gene transcription as assessed by reverse transcriptase-PCR (RT-PCR) with that measured by Northern analysis of parasite RNA. Phenotypically selected young parasites have multiple transcripts detected by RT-PCR, but the full-length transcript appears to be homogeneous. In addition, we demonstrate that the choice of primers used for RT-PCR is crucial in data interpretation.

This new feature in Parasitology Today will host reports from the laboratories involved in genomics of parasites, be that sequencing, mapping or ‘functional genomics’ – the mining and analysis of the sequence datasets, and the development of postgenomics tools to examine gene expression, response to drugs and population variability. It will publicize new technology to wider audiences, let communities of researchers know about novel resources (particularly those available through the World Wide Web) and highlight significant advances in the understanding of parasitic genomes through functional genomics.

Orlando, FL, USA

December 1997